JP6007106B2 - 炎症性腸疾患(ibd)及び過敏性腸症候群(ibs)の予防及び治療のための組換体プロバイオティック細菌 - Google Patents
炎症性腸疾患(ibd)及び過敏性腸症候群(ibs)の予防及び治療のための組換体プロバイオティック細菌 Download PDFInfo
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Description
本明細書で使用するとき、WAP族の用語「トラッピン−2」(エラフィン、エラスターゼ特異的阻害剤(ESI)又は皮膚抗−ロイコプロテアーゼに関するSKALPとしても知られる)とは、呼吸器官中で分泌される、HNE(ヒト好中球エラスターゼ)及びプロテイナーゼ3の低分子量(9.9kDa)の阻害剤を指す(Sallenaveら著、1991年及び1993年)。(A1−Pi;アルファ1−抗トリプシン)及びSLPI(分泌型白血球ペプチダーゼ阻害剤)と共に、トラッピン−2は、肺における「抗エラスターゼシールド」の不可欠な部分を含む。ヒトトラッピン−2遺伝子に関する代表的配列は、データベースGenbankに受託番号S58717で寄託されている。
蛋白質及びその使用法
食品グレード細菌
組成物
乳酸細菌におけるエラフィンのクローニング及び発現
動物
結腸炎の誘発及び研究設計
炎症パラメータの測定
結腸組織及び管腔洗浄液中のセリンプロテアーゼ活性
カラシ油に反応する内臓痛行動の誘起及び測定
統計値
結果
エラフィンを発現する組換体Lactococcus lactisが、マウスのDSS結腸炎の進行に対して保護すること
エラフィンを更に発現する組換体Lactobacillus caseiが、マウスのDSS結腸炎の進行に対して保護すること
エラフィンを発現する組換体Lactocuccus Lactisが、内臓痛行動を低減すること
htrA菌株による結果
比較による結果
L.lactisにおけるプロモーター亜鉛(PZn)zittR制御発現のEDTA誘導
参照文献
Braat,H.,M.P.PeppelenboschとD.W.Hommes著,2003年.「Interleukin−10−based therapy for inflammatory bowel disease」Expert.Opin.Biol.Ther.3:725−731頁.
Braat,H.,P.Rottiers,D.W.Hommes,N.Huyfhebaert,E.Remaut,J.P.Remon,S.J.van Deventer,S.Neirynck,M.P.Pepplenbosch,及びL.Steidler著,2006年.「A phase I trial with trangenic bacteri expressing interleukin−10 in Crohn’s diseases」.Clin.Gastroenterol.Hepatol.4:754−759頁.
Bron Peter A.,Marcos G.Benchimol,Jolanda Lambert,Emmanuelle Palumbo,Marie Deghorain,Jean Delcour,Willem M.de Vos,Michiel Kleerebezem,及びPascal Hols著,「USE of the alr Gene as a Food−Grade Selection Marker in Lactic Acid Bacteria」.Environmental Microbiology,2002年11月,5663−5670頁.
Cenac,N.,C.N.Andrew,M.Holzhausen,K.Chapman,G.Cottrell,P.Andrade−Gordon,M.Steinhoff,G.Barbara,P.Beck,N.W.Bunnett,K.A.Sharkey,J.G.Ferraz,E.Shaffer,及びN.Vergnolle著,2007年「Role for protease activity in visceral pain in irritable bowel syndrome」.J.Clin.Invest 117:636−647頁.
Hedin,C.,K.Whelan,及びJ.O.Lindsay著,2007年.「Evidence for the use of probiotics and prebiotecs in inflammatory bowel disease:a review of clinical trials.」Proc.Nutr.Soc.66:307−315頁.Sallenave,J.−M.Biol.Chem.Hoppe−Seyler 372(1991年),13−21頁.
Hyun,E.,P.Andrade−Gordon,M.Steinhoff,及びN.Vergnolle著,2008年.「Protease−activated receptor−2 activation:a major actor in intestinal inflammation」.Gut 57:1222−1229頁.
Llull D.及びI.Poquet著,「New Expression System Tightly Controlled by Zinc Availability in Lactococcus Lactis」.Environmental Microbiology,2004年9月,5398−5406頁.
Motta Jean−Paul,Laurent Magne,Delphyne Descamps,Corinne Rolland,Camila Squarzoni−Dale,Perrine Rousset,Laurence Martin,Nicolas Cenac,Viviane Balloy,Michel Huerre,Dieter Jenne,Julien Wartelle,Azzaq Belaaouaj,Emmanuel Masl,Jean−Pierre Vinel,Laurent Alric,Michel Chignard,Nathalie Vergnolle,Jean−Michel Sallenave著,「Modifying the protease,anti−protease pattern by elafin over−expression protects mice from colitis」.Gastroenterology 2011年、In Press.
Poquet I,Saint V,Seznec E,Simoes N,Bolotin A,Gruss A.著,「HtrA is the unique surface housekeeping protease in Lactococcus lactis and is required for natural protein processing」.Mol Microbiol.2000年3月;35(5):1042−51頁.
Sellenave JM,Silva A.,Marsden M.E.及びRyle A.P.著,Am.J.Respir.Cell Mol.Biol.8(1993年),126−133頁.
Sallenave JM著.「Secretory leuukocyte protease inhibitor and erafin/trappin−2:versatile mucosal antimicrobials and regulators of immunity」.Am J Respir Cell Mol Biol.2010年6月;42(6):635−43頁.Epub 2010年4月15日.Review.
Sartor,R.B.著2004年:「Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases:antibiotics,probiotics,and prebiotics」.Gastroenterology 126:1620−1633頁.
Salzman NH,Ghosh D,Huttner Km,Paterson Y,Bevins CL著.「Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin」.Nature.2003年4月3;422(6931):522−6頁
Simpson AJ,Maxwell AI,Govan JR,Haslett C,Sallenave JM著.「Elafin(elaastase−specific inhibitor)has anti−microbial activity against gram−positive and gram−negative respiratory pathogens」.FEBS Lett.1999年6月11日;452(3):309−13頁.
Steidler,L.,W.Hans,L.Schotte,S.Neirynck,F.Obermeier,W.Falk,W.Fiers,及びE.Remaut著.2000年.「Treatment of murine colitis by Lactococcus lactis secreting interleukin−10」.Science 289:1352−1355頁
Thierry Moreau,Kevin Baranger,Sebastien Dade,Sandrine Dallet−Choisy,Nicolas Guyot,Marie−Louise Zani著.「Muitifaceted roles og human elafin and secretory leukocyte proteinase inhibitor (SLPI),two serine protease inhibitor of the chelonianin family」Biochimie 90(2008年)284−295頁.
Vergnolle,N.著,2005年.「Clinical relevance of proteinase−activated receptors in the gut」.Gut 54:867−874頁.
Vergnolle,N.,L.Cellars,A.Mencarelli,G.Rizzo,S.Swaminathan,P.Beck,M.Steinhoff,P.Andrade−Gordon,N.W.Bunnett,M.D.Hollenberg,J.L.Wallace,G.Cirino,及びS.Fiorucci著.2004年.「A role for proteinase−activated recptor−1 in inflammatory bowel diseases」.J Clin Invest 114:1444−1456頁.
Claims (9)
- エラフィン蛋白質又はエラフィン蛋白質の活性フラクションをコードする組換体遺伝子を含み、Lactococcus lactisまたはLactobacillus caseiから選択される、組換体食品グレード乳酸細菌。
- 前記乳酸細菌が欠損栄養要求性遺伝子を含み、これによって、前記乳酸細菌の生存が、特異的化合物の存在に厳密に依存する、請求項1に記載の組換体食品グレード乳酸細菌。
- 前記欠損栄養要求性遺伝子がthyA遺伝子である、請求項2に記載の組換体食品グレード乳酸細菌。
- 前記選択された遺伝子が、前記欠損栄養要求性遺伝子の代わりに挿入される、請求項3に記載の組換体食品グレード乳酸細菌。
- htrA遺伝子が不活性化されたLactococcus lactisである、請求項1〜4のうちのいずれか一項に記載の組換体食品グレード乳酸細菌。
- 過敏性腸症候群の治療において使用するための、請求項1〜5のうちのいずれか一項に記載の組換体食品グレード乳酸細菌。
- 前記細菌が、被験者に粘膜投与、経口投与、鼻腔内投与または直腸投与されるよう意図されている、請求項6に記載の組換体食品グレード乳酸細菌。
- 請求項1〜7のうちのいずれか一項に記載の組換体食品グレード乳酸細菌を含む、過敏性腸症候群の治療において使用するための治療用組成物。
- 前記組成物が、被験者に粘膜投与、経口投与、鼻腔内投与または直腸投与されるよう意図されている、請求項8に記載の治療用組成物。
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Publication number | Priority date | Publication date | Assignee | Title |
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US9597379B1 (en) | 2010-02-09 | 2017-03-21 | David Gordon Bermudes | Protease inhibitor combination with therapeutic proteins including antibodies |
US8524220B1 (en) | 2010-02-09 | 2013-09-03 | David Gordon Bermudes | Protease inhibitor: protease sensitivity expression system composition and methods improving the therapeutic activity and specificity of proteins delivered by bacteria |
US8771669B1 (en) | 2010-02-09 | 2014-07-08 | David Gordon Bermudes | Immunization and/or treatment of parasites and infectious agents by live bacteria |
FR2990699B1 (fr) | 2012-05-21 | 2016-02-05 | Agronomique Inst Nat Rech | Cassettes d'expression procaryotes regulees par le stress |
WO2013188529A1 (en) * | 2012-06-15 | 2013-12-19 | Temple University Of The Commonwealth System Of Higher Education | Use of isolated bacterial amyloids for treatment of inflammatory disorders or diseases of the epithelium |
EP2706067A1 (en) * | 2012-09-06 | 2014-03-12 | Humboldt-Universität zu Berlin | Probiotic bacteria as carrier for a helminth-derived immunomodulator for the treatment of inflammatory disorders |
AU2013338774B2 (en) | 2012-11-01 | 2017-03-02 | Academisch Ziekenhuis Groningen | Methods and compositions for stimulating beneficial bacteria in the gastrointestinal tract |
US9593339B1 (en) | 2013-02-14 | 2017-03-14 | David Gordon Bermudes | Bacteria carrying bacteriophage and protease inhibitors for the treatment of disorders and methods of treatment |
EP2851086A1 (en) | 2013-09-20 | 2015-03-25 | Sanofi | Serpins: methods of therapeutic ß-cell regeneration and function |
EP2769732A1 (en) | 2013-02-22 | 2014-08-27 | Sanofi | Serpins: methods of therapeutic beta-cell regeneration and function |
US20160002316A1 (en) | 2013-02-22 | 2016-01-07 | Joslin Diabetes Center | Serpins: methods of therapeutic beta-cell regeneration and function |
AU2014226633A1 (en) | 2013-03-05 | 2015-09-03 | Academisch Ziekenhuis Groningen | Use of Faecali bacterium prausnitzii HTF-F (DSM 26943) to suppress inflammation. |
US9737592B1 (en) | 2014-02-14 | 2017-08-22 | David Gordon Bermudes | Topical and orally administered protease inhibitors and bacterial vectors for the treatment of disorders and methods of treatment |
WO2015168534A1 (en) * | 2014-05-02 | 2015-11-05 | Novogy, Inc. | Therapeutic treatment of gastrointestinal microbial imbalances through competitive microbe displacement |
KR101787543B1 (ko) | 2014-08-22 | 2017-10-19 | 샘표식품 주식회사 | 발효배양 산삼을 포함하는 항염증 조성물 |
WO2016124239A1 (en) * | 2015-02-04 | 2016-08-11 | Aurealis Oy | Recombinant probiotic bacteria for use in the treatment of a skin dysfunction |
CN105106246A (zh) * | 2015-08-20 | 2015-12-02 | 江南大学 | 一种植物乳杆菌zs2058及其用途 |
WO2017053349A1 (en) * | 2015-09-21 | 2017-03-30 | Vithera Pharmaceuticals, Inc. | Treatment of disease with lactic acid bacteria having stably integrated trappin-2 |
MA45288A (fr) * | 2016-06-08 | 2019-04-17 | Sofar Spa | Nouvelle utilisation médicale de probiotiques |
US10829563B2 (en) | 2016-06-16 | 2020-11-10 | INSERM (Institute National de la Santé et de la Recherche Médicale) | Method of screening a candidate compound for activity as an elastase 2A (ELA2A) inhibitor |
US11180535B1 (en) | 2016-12-07 | 2021-11-23 | David Gordon Bermudes | Saccharide binding, tumor penetration, and cytotoxic antitumor chimeric peptides from therapeutic bacteria |
US11129906B1 (en) | 2016-12-07 | 2021-09-28 | David Gordon Bermudes | Chimeric protein toxins for expression by therapeutic bacteria |
CN110331148B (zh) * | 2019-08-20 | 2021-05-04 | 华中农业大学 | 一种编码IFNα蛋白的基因、重组载体pELSH-IFNα、重组干酪乳杆菌及应用 |
US20220395489A1 (en) * | 2019-10-29 | 2022-12-15 | The Regents Of The University Of California | Therapeutic approach for treating inflammatory bowel disease |
KR20210129516A (ko) * | 2020-04-20 | 2021-10-28 | 주식회사 리비옴 | 혈관 작동성 장 펩티드를 발현하는 미생물, 및 그의 용도 |
CN111617099B (zh) * | 2020-06-16 | 2022-12-20 | 青岛农业大学 | 一种无抗高细胞亲和性结肠炎修复剂与应用方法 |
WO2022049273A1 (en) * | 2020-09-07 | 2022-03-10 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods of treatment of inflammatory bowel diseases |
CN113684162B (zh) * | 2021-06-03 | 2024-02-27 | 江南大学 | 一种表达小鼠防御素mBD14基因的重组植物乳杆菌及其应用 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5734014A (en) * | 1992-08-11 | 1998-03-31 | Tsumura & Co. | Elafin derivative |
IT1270123B (it) * | 1994-10-05 | 1997-04-28 | Dompe Spa | Composizioni farmaceutiche contenenti microorganismi ingegnerizzati e loro uso per terapia |
JPH10127292A (ja) * | 1996-10-31 | 1998-05-19 | Tsumura & Co | エラフィン類発現ベクターおよびこれを利用したエラフィン類の製造法 |
FR2787810B1 (fr) | 1998-12-24 | 2002-10-31 | Inst Nat De La Rech Agronomique Inra | Bacteries a gram positif depourvues d'activite proteasique htra, et leurs utilisations |
DE10101793A1 (de) * | 2001-01-17 | 2002-08-01 | Manfred Nilius | Verwendung von SLPI zur Behandlung chronisch-entzündlicher Darmerkrankungen |
EP1227152A1 (en) * | 2001-01-30 | 2002-07-31 | Société des Produits Nestlé S.A. | Bacterial strain and genome of bifidobacterium |
US7780961B2 (en) * | 2001-05-03 | 2010-08-24 | Actogenix N.V. | Self-containing Lactococcus strain |
CA2489930A1 (en) * | 2002-06-19 | 2003-12-31 | Vlaams Interuniversitair Instituut Voor Biotechnologie Vzw | Methods and means to promote gut absorption |
FR2843973B1 (fr) | 2002-08-30 | 2006-07-07 | Agronomique Inst Nat Rech | Cassettes d'expression procaryotes regulees par le zinc |
CA2506031A1 (en) * | 2002-11-15 | 2004-06-03 | Vib Vzw | Self-containing lactobacillus strain comprising a thya mutation and therapeutic applications thereof |
ES2381644T3 (es) * | 2004-03-24 | 2012-05-30 | Tripath Imaging, Inc. | Métodos y composiciones para la detección de enfermedades de cuello uterino |
CN101052705A (zh) * | 2004-05-18 | 2007-10-10 | 佛兰芒语埋葬-大学生物技术研究所Vzw | 自身遏制性乳杆菌菌株 |
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AU2011206532B2 (en) | 2015-07-30 |
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BR112012016982A2 (pt) | 2016-12-13 |
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CA2786847A1 (en) | 2011-07-21 |
US20130344033A1 (en) | 2013-12-26 |
US9688742B2 (en) | 2017-06-27 |
BR112012016982B8 (pt) | 2022-12-20 |
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AU2011206532A8 (en) | 2015-08-06 |
CN102740867A (zh) | 2012-10-17 |
WO2011086172A1 (en) | 2011-07-21 |
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